Crucial role of HMGA1 in the self-renewal and drug resistance of ovarian cancer stem cells

Cancer stem cells are a subpopulation of cancer cells characterized by self-renewal ability, tumorigenesis and drug resistance. The aim of this study was to investigate the role of HMGA1, a chromatin remodeling factor abundantly expressed in many different cancers, in the regulation of cancer stem cells in ovarian cancer. Spheroid-forming cancer stem cells were isolated from A2780, SKOV3 and PA1 ovarian cancer cells by three-dimensional spheroid culture. Elevated expression of HMGA1 was observed in spheroid cells along with increased expression of stemness-related genes, such as SOX2, KLF4, ALDH, ABCB1 and ABCG2. Furthermore, spheroid A2780 cells, compared with adherent cells, showed higher resistance to chemotherapeutic agents such as paclitaxel and doxorubicin. HMGA1 knockdown in spheroid cells reduced the proliferative advantage and spheroid-forming efficiency of the cells and the expression of stemness-related genes. HMGA1 overexpression in adherent A2780 cells increased cancer stem cell properties, including proliferation, spheroid-forming efficiency and the expression of stemness-related genes. In addition, HMGA1 regulated ABCG2 promoter activity through HMGA1-binding sites. Knockdown of HMGA1 in spheroid cells reduced resistance to chemotherapeutic agents, whereas the overexpression of HMGA1 in adherent ovarian cancer cells increased resistance to chemotherapeutic agents in vitro. Furthermore, HMGA1-overexpressing A2780 cells showed a significant survival advantage after chemotherapeutic agent treatment in a xenograft tumorigenicity assay. Together, our results provide novel insights regarding the critical role of HMGA1 in the regulation of the cancer stem cell characteristics of ovarian cancer cells, thus suggesting that HMGA1 may be an important target in the development of therapeutics for ovarian cancer patients.

Related Factors of Physical Function in a Rural Aged People

BACKGROUNDS: To investigate the physical functioning state of the rural aged people and its related factors. METHODS: 458 older people aged 65 years or older living in a rural area were interviewed fromAug. 6 to Aug. 9, 2003. Socioeconomic characteristics, structural and functional social supports, chronic disease, stress, and obesity(using body mass index) were included to explore their influencing physical functioning. Physical functioning was measured by Physical Functioning(PF) scale constructed by 2-factor(mobility and self-care). Cronbach's alpha of social support and PF scales were 0.91, 0.89 respectively. After univariate analysis, multiple regression analysis was conducted to identify major contributing factors to physical functioning. RESULTS: 1) Person of younger age, higher education level, having job, higher economic status were more likely to show a higher degree of physical functioning in both male and female. 2) In those who having spouse, the physical functioning scores were significantly higher. And the aged people with high social support got higher physical functioning score. 3) In male with diabetes, physical functioning score were significantly lower. In female with arthritis, physical functioning score were significantly lower. 4) For the aged people which having higher stress, the physical function wasn't good. 5) In multiple regression analysis, for both male and female, physical functioning of those who have no job, lower social support, higher stress was bad. In male with chronic disease and female with arthritis, the physical functional score was lower. CONCLUSION: The physical functioning of some rural aged people were affected by various factors such as social, psychological, economic and physical factors. So diverse policy and programwill be necessary for improve physical functioning of rural older people.

Evaluation of Shoulder Function Before and After Removal of Humeral Interlocking Nail / 대한정형외과학회잡지

PURPOSE: We evaluated the shoulder function according to the degree of protrusion or sinking of proximal ends of humeral interlocking nails. MATERIALS AND METHODS: On 12 patients who were treated using humeral antegrade intramedullary nailing, the shoulder function has been evaluated with the Constant's shoulder function score and the shoulder score index of the research of American Shoulder and Elbow Surgeons, before removal of nails and one year after that. The degree of protrusion or sinking of the proximal ends of nails was measured on shoulder AP X-ray films. Patients with shoulder dysfunction or neurovascular injuries were excluded from this study. RESULTS: Protrusion of the proximal end of the nail caused rotator cuff irritation and impingement and shoulder dysfunction. In the case of sinking of the proximal end of the nail, the shoulder function status was decreased with the sinking degree of the proximal end of it after nail removal. CONCLUSION: We thought that an accurate preoperative measurement of the nail length is needed and sinking the proximal end of nail minimally, simultaneously avoiding the protrusion, is important for the restoration of shoulder function after nail removal.